We report the first case in Europe of co-infection with disseminated cryptococcosis and histoplasmosis. The diagnosis of invasive histoplasmosis was confirmed by microscopic examination of the anatomic right colon specimen (hemicolectomy). Histoplasma antigen detection is not yet available in France but it could have a key role in the early diagnosis of disseminated histoplasmosis co-existing with a cryptococcal infection, especially in HIV-infected African people.